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Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members

Vagin, Vasily V. and Wohlschlegel, James and Qu, Jun and Jonsson, Zophonias and Huang, Xinhua and Chuma, Shinichiro and Girard, Angelique and Sachidanandam, Ravi and Hannon, Gregory J. and Aravin, Alexei A. (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes and Development, 23 (15). pp. 1749-1762. ISSN 0890-9369. PMCID PMC2720255.

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In germ cells, Piwi proteins interact with a specific class of small noncoding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. Basic models describe the overall operation of piRNA pathways. However, the protein compositions of Piwi complexes, the critical protein–protein interactions that drive small RNA production and target recognition, and the precise molecular consequences of conserved localization to germline structures, call nuage, remains poorly understood. We purified the three murine Piwi family proteins, MILI, MIWI, and MIWI2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with PRMT5/WDR77, an enzyme that dimethylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their N termini. These modifications are essential to direct complex formation with specific members of the Tudor protein family. Recognition of methylarginine marks by Tudor proteins can drive the localization of Piwi proteins to cytoplasmic foci in an artificial setting, supporting a role for this interaction in Piwi localization to nuage, a characteristic that correlates with proper operation of the piRNA pathway and transposon silencing in multiple organisms.

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Additional Information:© 2009 by Cold Spring Harbor Laboratory Press. Freely available online through the Genes & Development Open Access option. Received April 24, 2009; revised version accepted June 8. 2009. Published in Advance July 7, 2009. We thank S.L. Martin, J. Wang, B.R. Cullen, A. Bortvin, and M. Fritzler for sharing antibodies, and N. Nakatsuji, T. Tanaka, and M. Hosokawa for tissues and Tudor mutant animals. We thank Sang Yong Kim (CSHL) for generating transgenic animals. We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology, and Michelle Rooks, Dick Mccombie, Danea Rebbolini, and Laura Cardone for help with Illumina sequencing. We thank Katalin Fejes Toth, Nikolay Rozhkov, and Antoine Molaro for help with experiments and illustrations, and Assaf Gordon for help with data analysis. S.C. is supported by Grants-in-Aid from MEXT, Japan; J.W. was supported by funds from the Jonsson Cancer Center at UCLA; and J.Q. is supported by the University at Buffalo Center of Protein Therapeutics grant. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by a kind gift from Kathryn W. Davis and grants from the National Institutes of Health to G.J.H., and an NIH Pathway to Independence Award K99HD057233 to A.A.A.
Funding AgencyGrant Number
Ministry of Education, Culture, Sports, Science and Technology (MEXT)UNSPECIFIED
University of California Los Angeles (UCLA)UNSPECIFIED
University at BuffaloUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:Arginine methyation; piRNAs; transposon silencing; tudor proteins
Issue or Number:15
PubMed Central ID:PMC2720255
Record Number:CaltechAUTHORS:20190508-112900956
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95349
Deposited By: Tony Diaz
Deposited On:09 May 2019 17:48
Last Modified:03 Oct 2019 21:12

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